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Hyperthyroidism Microchapters

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Differentiating hyperthyroidism from other diseases


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2] 'For the WikiDoc patient information for this topic, click here


Thyroid hormones are responsible for regulating the basal metabolic rate of the body. Over secretion of thyroid hormones can lead to a wide variety of syndromes depending on the cause of the hyperthyroidism. Hyperthyroidism can be due to hyperactivity of the thyroid gland itself (primary hyperthyroidism) or due to abnormalities in the pituitary gland or the hypothalamus causing irregularities in the upper control of the gland. Hyperthyroidism can also be classified according to the results of iodine uptake study into high uptake, high or normal uptake, and low uptake. Hyperthyroidism must be differentiated from other diseases that cause insomnia, anxiety, and hypertension such as pheochromocytoma, generalized anxiety disorder, and essential hypertension. The pathophysiology and the compilation of symptoms and signs differ between the different diseases causing high thyroid activity.


According to the origin of the abnormality

Hyperthyroidism is classified according to the origin of the lesion into primary, secondary, and tertiary hyperthyroidism.[1]

According to the origin of the abnormality
Primary hyperthyroidism
Secondary hyperthyroidism
Tertiary hyperthyroidism
Grave’s disease
Toxic thyroid nodule
Thyroid adenoma
Multinodular goiter
Pituitary adenoma
Intracranial tumors pressing pituitary gland
Intracranial tumors or masses involving hypothalamus

According to iodine uptake

Hyperthyroidism can be classified according to the results of iodine uptake test into high uptake, high or normal uptake, and low uptake.[2]

According to iodine uptake
High uptake
High or normal uptake
Low uptake
Graves' disease
Toxic multinodular goiter
Toxic thyroid adenoma
• Iodine caused hyperthyroidism
Germ cell tumors (choriocarcinoma in males and testicular germ cell tumors)
Pituitary TSH producing adenoma
Subacute thyroiditis
• Hyperthyroidism due to ectopic thyroid tissue
• Factitious thyrotoxicosis
Struma ovarii
• Painless thyroiditis
• Amiodarone induced thyroiditis-Type 1
• Amiodarone induced thyroiditis-Type 2

Differentiating hyperthyroidism from other diseases

Hyperthyroidism must be differentiated from other diseases that cause anxiety, elevated blood pressure, and insomnia; such as essential hypertension, generalized anxiety disorder, and pheochromocytoma.

Disease Prominent clinical features Investigations
Hyperthyroidism The main symptoms include:
Essential hypertension Most patients with hypertension are asymptomatic at the time of diagnosis.

Common symptoms are listed below:

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 express) recommends the following routine laboratory tests before initiation of therapy for hypertension:
Generalized anxiety disorder According to DSM V, the following criteria should be present to fit the diagnosis of generalized anxiety disorder:
  1. The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
  2. Difficulty to control the apprehension
  3. Associated restless, fatigue, irritability, difficulty concentration, muscle tension or sleep disturbance (only one of these manifestations)
  4. The anxiety or the physical manifestations must affect the social and the daily life of the patient
  5. Exclusion of another medical condition or the effect of another administered substance
  6. Exclusion of another mental disorder causing the symptoms
Menopause The perimenopausal symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of estrogens, progestin, and testosterone. Some of these symptoms such as formication etc may be associated with the hormone withdrawal process.
  • B-HCG should always be done first to rule out pregnancy, especially in women under the age of 45 years.
  • FSH can be measured but it can be falsely normal or low.
  • TSH, T3, and T4 should be assessed to rule out thyroid abnormalities.
  • Prolactin can be measured to rule out prolactinoma, as a cause of menopause.
Opioid withdrawal disorder According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:
  1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e., several weeks or longer) or administration of an opioid antagonist after a period of opioid use.
  2. Development of three or more of the following criteria minutes to days after cessation of drug use: Dysphoric mood, nausea or vomiting, muscle aches, Lacrimation or rhinorrhea, pupillary dilation, piloerection, or sweating, diarrhea, yawning, fever, and insomnia.
  3. The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
  4. The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
Pheochromocytoma The hallmark symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include:
  • Palpitations, especially in epinephrine producing tumors
  • Anxiety often resembling that of a panic attack
  • Sweating
  • Headaches occur in 90 % of patients.
  • Paroxysmal attacks of hypertension, but some patients have normal blood pressure
  • It may be asymptomatic and discovered by incidence screening especially MEN patients

Please note that not all patients with pheochromocytoma experience all classical symptoms.

Diagnostic lab findings associated with pheochromocytoma include:

Differentiating the causes of thyrotoxicosis

Cause of thyrotoxicosis TSH receptor antibodies Thyroid US Color flow Doppler Radioactive iodine uptake/Scan Other features
Graves' disease + Hypoechoic pattern Ophthalmopathy, dermopathy, acropachy
Toxic nodular goiter - Multiple nodules - Hot nodules at thyroid scan -
Toxic adenoma - Single nodule - Hot nodule -
Subacute thyroiditis - Heterogeneous hypoechoic areas Reduced/absent flow Neck pain, fever, and
elevated inflammatory index
Painless thyroiditis - Hypoechoic pattern Reduced/absent flow -
Amiodarone induced thyroiditis-Type 1 - Diffuse or nodular goiter ↓/Normal/↑ ↓ but higher than in Type 2 High urinary iodine
Amiodarone induced thyroiditis-Type 2 - Normal Absent ↓/absent High urinary iodine
Central hyperthyroidism - Diffuse or nodular goiter Normal/↑ Inappropriately normal or high TSH
Trophoblastic disease - Diffuse or nodular goiter Normal/↑ -
Factitious thyrotoxicosis - Variable Reduced/absent flow ↓ Serum thyroglobulin
Struma ovarii - Variable Reduced/absent flow Abdominal RAIU

Prominent features in the different causes of hyperthyroidism

Disease Findings
Thyroiditis Direct chemical toxicity with inflammation Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.[3][4]
Radiation thyroiditis Patients treated with radioiodine may develop thyroid pain and tenderness 5 to 10 days later, due to radiation-induced injury and necrosis of thyroid follicular cells and associated inflammation.
Drugs that interfere with the immune system Interferon-alfa is a well-known cause of thyroid abnormality. It mostly leads to the development of de novo antithyroid antibodies.[5]
Lithium Patients treated with lithium are at a high risk of developing painless thyroiditis and Graves' disease.
Palpation thyroiditis Manipulation of the thyroid gland during thyroid biopsy or neck surgery and vigorous palpation during the physical examination may cause transient hyperthyroidism.
Exogenous and ectopic hyperthyroidism Factitious ingestion of thyroid hormone The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[6]
Acute hyperthyroidism from a levothyroxine overdose The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.[7]
Struma ovarii Functioning thyroid tissue is present in an ovarian neoplasm.
Functional thyroid cancer metastases Large bony metastases from widely metastatic follicular thyroid cancer cause symptomatic hyperthyroidism.
Hashitoxicosis It is an autoimmune thyroid disease that initially presents with hyperthyroidism and a high radioiodine uptake caused by TSH-receptor antibodies similar to Graves' disease. It is then followed by the development of hypothyroidism due to the infiltration of the thyroid gland with lymphocytes and the resultant autoimmune-mediated destruction of thyroid tissue, similar to chronic lymphocytic thyroiditis.[8]
Toxic adenoma and toxic multinodular goiter Toxic adenoma and toxic multinodular goiter are results of focal/diffuse hyperplasia of thyroid follicular cells independent of TSH regulation. Findings of single or multiple nodules are seen on physical examination or thyroid scan.[9]
Iodine-induced hyperthyroidism It is uncommon but can develop after an iodine load, such as administration of contrast agents used for angiography or computed tomography (CT), or iodine-rich drugs such as amiodarone.
Trophoblastic disease and germ cell tumors Thyroid-stimulating hormone and HCG have a common alpha-subunit and a beta-subunit with considerable homology. As a result, HCG has weak thyroid-stimulating activity and high titer HCG may mimic hyperthyroidism.[10]


Rgulation of thyroxin secretion - By CFCF; slightly modified by Geo-Science-International - This file was derived from Thyroid vector.svg:, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=47043638


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